{"id":67331,"date":"2026-06-12T01:17:35","date_gmt":"2026-06-11T23:17:35","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/06\/12\/dna-hypomethylating-agents-preserve-t-cell-stemness-and-potentiate-the-efficacy-of-cd3-bispecific-antibodies\/"},"modified":"2026-06-12T01:17:35","modified_gmt":"2026-06-11T23:17:35","slug":"dna-hypomethylating-agents-preserve-t-cell-stemness-and-potentiate-the-efficacy-of-cd3-bispecific-antibodies","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/06\/12\/dna-hypomethylating-agents-preserve-t-cell-stemness-and-potentiate-the-efficacy-of-cd3-bispecific-antibodies\/","title":{"rendered":"DNA hypomethylating agents preserve T cell stemness and potentiate the efficacy of CD3-bispecific antibodies"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Jun 11. doi: 10.1158\/2326-6066.CIR-25-1420. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Bispecific antibodies targeting tumor-associated antigens and CD3 are promising therapeutic agents for both solid and hematologic cancers. CD3-bispecifics induce T cell activation and cytotoxicity; however, prolonged TCR stimulation can lead to chromatin rewiring and T cell dysfunction, thereby limiting their full therapeutic potential. Here, we investigate the combination of CD3-bispecifics with the DNA hypomethylating agent decitabine and observe enhanced synergistic tumor growth inhibition in various preclinical models. Utilizing a PSMAxCD3 bispecific antibody for treatment of prostate carcinoma and in vivo humanized mouse disease models, we catalog, at the single-cell level, the dynamics of T cell epigenetic states during bispecific therapy and in combination with decitabine. Importantly, this combination strategy preserves a TCF-1+ T cell population and delays acquisition of a dysfunctional state at both chromatin and protein levels. At the DNA methylation level, TCR stimulation in the presence of decitabine maintains a naive-like pattern in gene loci associated with T cell stemness. This study provides a resource for understanding the evolution of T cell states during immunotherapy and mechanistic support for combining epigenetic modifiers with CD3-bispecifics in the clinic.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42275524\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260611191735&amp;v=2.20.0\">42275524<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-1420\">10.1158\/2326-6066.CIR-25-1420<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Jun 11. doi: 10.1158\/2326-6066.CIR-25-1420. Online ahead of print. ABSTRACT Bispecific antibodies targeting tumor-associated antigens and CD3 are promising therapeutic agents for both solid and hematologic cancers. CD3-bispecifics induce T cell activation and cytotoxicity; however, prolonged TCR stimulation can lead to chromatin rewiring and T cell dysfunction, thereby limiting their full therapeutic &#8230; <a title=\"DNA hypomethylating agents preserve T cell stemness and potentiate the efficacy of CD3-bispecific antibodies\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/06\/12\/dna-hypomethylating-agents-preserve-t-cell-stemness-and-potentiate-the-efficacy-of-cd3-bispecific-antibodies\/\" aria-label=\"Read more about DNA hypomethylating agents preserve T cell stemness and potentiate the efficacy of CD3-bispecific antibodies\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-67331","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/67331","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=67331"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/67331\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=67331"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=67331"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=67331"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}